阑尾源性腹膜假黏液瘤单中心诊疗经验

  目的   总结细胞减灭术加腹腔热灌注化疗（cytoreductive surgery & hyperthermic intraperitoneal chemotherapy，CRS+HIPEC）治疗阑尾源性腹膜假黏液瘤（pseudomyxoma peritonei，PMP）的单中心诊疗经验。   方法   回顾性分析2012年1月至2018年12月于航天中心医院收治，病理证实为阑尾源性PMP并经CRS+HIPEC治疗604例患者的临床数据，进行统计学分析。   结果   604例患者经历621次CRS+HIPEC治疗，平均年龄56.7岁，其中女性364例（60.3%），男性240例（39.7%），平均腹膜癌指数（peritoneal cancer index，PCI）为25.7。28.5%（172/604）的患者完全减瘤（CCR 0/1）。3~4级不良事件发生率为21.7%（131/604），围手术期死亡率为0.7%（4/604），术后5年生存率为53.6%。高级别病理类型、不完全减瘤（CCR 2/3）、PCI>20、3~4级不良事件是PMP患者预后不良的独立危险因素。   结论   阑尾源性PMP临床罕见，治疗方法特殊，对于怀疑或确诊PMP的患者，尽早行规范CRS+HIPEC治疗，有望取得良好的预后。      

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

CT模拟与三维计划对减低鼻咽癌放疗并发症的价值

目的了解引起鼻咽癌放射治疗并发症的影响因素,通过观察CT模拟及三维计划与X线模拟二维计划比较分析对鼻咽癌放射并发症的影响.方法临床观察从1995年～2005收治的并且能够随诊到的161例鼻咽癌病人放疗后出现的并发症.临床从张口受限、急性皮肤反应、颈部组织纤维化、口干症以及鼻腔粘连等并发症来观察结果.结果颈部组织纤维化中、重度,三维计划分别为8/108(7.4%)和1/108(0.9%);二维计划分别为8/53(15.1%)和4/53(7.5%).口干症中、重度三维计划分别为10/108(9.3%)和3/108(2.8%);二维计划分别为17/53(32.1%)和9/53(17.0%).急性皮肤反应中、重度三维计划分别为18/108(16.7%)和8/108(7.4%);二维计划分别为19/53(35.8%)和11/53(20.8%).张口受限三维计划为7/108(6.5%);二维计划为12/53(22.6%).鼻腔粘连三维计划为12/108(11.1%),二维计划为13/53(24.5%).结论CT模拟与三维计划可明显降低放疗并发症的发生.     

Electronic properties of PbCl2 and PbBr2 using Compton scattering technique

We present the electron momentum densities of PbCl₂ and PbBr₂ using 661.65 keV γ-rays from 20 Ci ¹³⁷Cs source. To supplement our experimental investigations, we also report energy bands, density of states, Mulliken's population and Compton profiles of PbCl₂ and PbBr₂ using linear combination of atomic orbitals within Hartree–Fock and density functional theories. The energy bands are also computed employing full potential linearized augmented plane wave (FP-LAPW) method. Compton profiles are also analyzed in terms of equal-valence-electron-density scale. It shows that PbCl₂ is more covalent than PbBr₂, which is in agreement with the Mulliken's population analysis. It is seen that the Hartree–Fock and density functional theory based Compton line shapes show similar type of deviations from the experimental data. The luminescence properties of these halides are explained on the basis of energy band and density of states.     

临床护士锐器伤调查与预防

目的探讨护士预防锐器伤的对策。方法对某所综合性医院193名护士在2004年1月~2005年6月发生的锐器伤进行问卷调查。结果46.1%护士发生锐器伤,人均1.6次;发生锐器伤的锐器主要是注射器针头(36.7%),其次是玻璃(32.4%);护士主要在掰安瓿(29.5%)、使用后处理锐器(22.3%)、安装调整针头(15.8%)、医护配合传递锐器(10.1%)等环节容易发生锐器伤;有79.1%护士发生锐器伤时未戴手套。结论护士面临锐器伤职业危险,各方应当采取对策,预防和控制锐器伤。